Essential control of early B-cell development by Mef2 transcription factors

Herglotz J, Unrau L, Hauschildt F, Fischer M, Kriebitzsch N, Alawi M, Indenbirken D, Spohn M, Mueller U, Ziegler M, Schuh W, Jäck HM, Stocking C (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Blood American Society of Hematology

Book Volume: 127

Pages Range: 572-81

Journal Issue: 5

DOI: 10.1182/blood-2015-04-643270

Abstract

The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms involved in initiating downstream programs are incompletely understood. The pre-B-cell receptor (pre-BCR) is an important checkpoint of B-cell development and is essential for a pre-B cell to traverse into an immature B cell. Here, we show that activation of myocyte enhancer factor 2 (Mef2) transcription factors (TFs) by the pre-BCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the pre-B-cell stage in mice deficient for Mef2c and Mef2d TFs and that pre-BCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the Erk5 mitogen-activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development.

Authors with CRIS profile

Wolfgang Schuh Department of Molecular Immunology Hans-Martin Jäck Department of Molecular Immunology

Involved external institutions

Heinrich-Pette-Institut (HPI), Leibniz-Institut für Experimentelle Virologie / Heinrich Pette Institute – Leibniz Institute for Experimental Virology DE Germany (DE)

How to cite

APA:

Herglotz, J., Unrau, L., Hauschildt, F., Fischer, M., Kriebitzsch, N., Alawi, M.,... Stocking, C. (2016). Essential control of early B-cell development by Mef2 transcription factors. Blood, 127(5), 572-81. https://dx.doi.org/10.1182/blood-2015-04-643270

MLA:

Herglotz, Julia, et al. "Essential control of early B-cell development by Mef2 transcription factors." Blood 127.5 (2016): 572-81.

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